Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion

Cioni, Bianca; Zaalberg, Anniek; Beijnum, Judy R. van; Melis, Monique; Burgsteden, Johan van; Muraro, Mauro J.; Hooijberg, Erik; Peters, Dennis; Hofland, Ingrid; Lubeck, Yoni; Jong, Jeroen de; Sanders, Joyce; Vivié, Judith; Poel, Henk G. van der; Boer, Jan Paul de; Griffioen, Arjan W.; Zwart, Wilbert; Bergman, Andries M.

doi:10.1038/s41467-020-18313-y

Cited by 82 publications

(75 citation statements)

References 64 publications

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“…The TME and immune-related biomarkers play essential roles in the precise treatment of some cancers [22]. The TME, including immune cells, stromal cells, and cytokines, has been proven to determine the biological behavior of cancer cells [23][24][25]. Infiltrating immune and stromal cells account for the majority of normal cells in solid tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Jiang

Zhu³

et al. 2021

Cancer Cell Int

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Methyltransferase-like 7B (METTL7B) is a member of the methyltransferase-like protein family that plays an important role in the development and progression of tumors. However, its prognostic value and the correlation of METTL7B expression and tumor immunity in some cancers remain unclear. By analyzing online data, we found that METTL7B is abnormally overexpressed in multiple human tumors and plays an important role in the overall survival (OS) of patients with 8 cancer types and disease-free survival (DFS) of patients with 5 cancer types. Remarkably, METTL7B expression was positively correlated with the OS and DFS of patients with lower-grade glioma (LGG). In addition, a positive correlation between METTL7B expression and immune cell infiltration in LGG was observed. Moreover, we identified a strong correlation between METTL7B expression and immune checkpoint gene expression in kidney chromophobe (KICH), LGG and pheochromocytoma and paraganglioma (PCPG). Furthermore, METTL7B was involved in the extracellular matrix (ECM) and immune-related pathways in LGGs. Finally, in vitro experiments showed that knockdown of METTL7B inhibited the growth, migration, invasion and the epithelial–mesenchymal transition (EMT) of LGG cells. METTL7B expression potentially represents a novel prognostic biomarker due to its significant association with immune cell infiltration in LGG.

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Section: Discussionmentioning

confidence: 99%

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Jiang

Zhu³

et al. 2021

Cancer Cell Int

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“…The contributing role(s) of the androgen receptor in BPH is not fully understood, and the involvement of androgen receptor signaling in prostatic inflammation may contribute to this complexity (48,49). Reduced circulating androgen levels in aging men might contribute to .…”

Section: Discussionmentioning

confidence: 99%

“…The immunosuppressive function of androgens has been reported in numerous studies ( 32 ). The contributing role(s) of the androgen receptor in BPH is not fully understood, and the involvement of androgen receptor signaling in prostatic inflammation may contribute to this complexity ( 48, 49 ). Reduced circulating androgen levels in aging men might contribute to increased inflammation in BPH, but whether the increase in inflammation is in response to a stimulus (e.g.…”

Section: Discussionmentioning

confidence: 99%

TNF Blockade Reduces Prostatic Hyperplasia and Inflammation while Limiting BPH Diagnosis in Patients with Autoimmune Disease

Vickman

Aaron‐Brooks

Zhang

et al. 2021

Preprint

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Benign prostatic hyperplasia (BPH) is ostensibly linked to autoimmune (AI) diseases, but whether the prostate is a target of systemic inflammation associated with AI conditions is unknown. Prostatic inflammation is linked to fibrosis, hyperplasia, and reduced responses to BPH-related medical therapies. This study was conducted to determine if AI disease correlates with BPH diagnosis and whether systemic targeting of an inflammatory mediator limits prostatic inflammation and hyperplasia. Patient medical records (n=112,152) were evaluated to determine BPH prevalence among different AI diseases. Inflammatory cells from human BPH tissues were analyzed by single-cell (sc)RNA-seq and the tumor necrosis factor (TNF)α-antagonist etanercept was tested in two murine models of prostatic enlargement. BPH prevalence was significantly higher among patients with AI disease compared to unaffected individuals. However, AI patients treated with TNFα-antagonists had a significantly reduced incidence of BPH. Data from scRNA-seq identified macrophages as a dominant source of TNFα and in vitro assays confirmed that TNFα stimulates BPH-derived fibroblast proliferation. In the AI patient cohort and murine models, systemic treatment with TNFα-antagonists decreased prostatic epithelial proliferation, macrophage infiltration, and epithelial NFκB activation compared to control tissues. These studies are the first to show that patients with AI diseases have a heightened susceptibility to BPH and that the TNFα-signaling axis is important for BPH pathogenesis. Macrophage-secreted TNFα may mechanistically drive BPH via chronic activation of the signaling axis and NFκB. TNFα blockade appears to be a promising new pharmacological approach to target inflammation and suppress BPH.

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“…In addition, signaling via TREM-1 is significantly related to the development and progression of chronic lymphocytic leukemia ( 15 ). TREM-1 is induced in macrophages by the androgen receptor signaling pathway in prostate cancer, and increases the motility and invasive capacity of prostate cancer cells ( 16 ). In recent years, many studies have suggested various strategies for regulating TREM-1 expression and activity to block the interaction between TREM-1 and its ligands to treat a number of diseases, including cancer ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Prognostic Value and Potential Molecular Mechanisms of TREM-1 Overexpression in Papillary Thyroid Cancer via Bioinformatics Methods

Xie

et al. 2021

Front. Endocrinol.

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BackgroundTriggering receptor expressed on myeloid cells-1 (TREM-1) has been reported as a biomarker in many cancers. However, the biological function of TREM-1 in papillary thyroid carcinoma (PTC) remains unknown.MethodsWe obtained TREM-1 expression data from The Cancer Genome Atlas (TCGA) database. Enrichment analysis of coexpressed genes and TREM-1 methylation analysis were performed via LinkedOmics. The correlations between TREM-1 and immune infiltrates were investigated via ESTIMATE, TIMER and TISIDB. We analyzed the association of TREM-1 expression with pan-cancer overall survival via Gene Expression Profiling Interactive Analysis (GEPIA).ResultsTREM-1 has lower methylation levels and higher expression levels in PTC tissues compared to normal tissues. TREM-1 expression is significantly associated with poor prognosis, advanced T classification, advanced N classification, and an increased incidence of BRCA2 and BRAF mutations. Genes coexpressed with TREM-1 primarily participate in immune-related pathways. TREM-1 expression is positively correlated with immune infiltration, tumor progression and poor overall survival across cancers.ConclusionsTREM-1 is a good prognostic and diagnostic biomarker in PTC. TREM-1 may promote thyroid cancer progression through immune-related pathways. Methylation may act as an upstream regulator of TREM-1 expression and biological function. Additionally, TREM-1 has broad prognostic value in a pan-cancer cohort.

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Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion

Cited by 82 publications

References 64 publications

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

TNF Blockade Reduces Prostatic Hyperplasia and Inflammation while Limiting BPH Diagnosis in Patients with Autoimmune Disease

Analysis of the Prognostic Value and Potential Molecular Mechanisms of TREM-1 Overexpression in Papillary Thyroid Cancer via Bioinformatics Methods

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